Silica-based fluorescent nanoparticles

Abstract

A composition including the reaction product of: an organic silane of Formula SiR 1 m X 1 4-m ; a fluorescent dye-silane compound of Formula D-L′-(CH 2 ) n —SiX 2 3 ; water; and a hydrolysis catalyst; where R 1 is a C 1 -C 6 alkyl that is unsubstituted or substituted with one or more halogens or hydroxyl group, C 2 -C 6 alkenyl that is unsubstituted or substituted with one or more halogens or hydroxyl group, or an aryl group that is unsubstituted or substituted with one or more halogens or hydroxyl group, m is 0 or 1; n is 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, D is a radical having a fluorophore; L1 is a bond, O, S, C(O)O, C(O)NR 2 , SO 2 O, C(O)S, C(S), or S 2 ; R 2 is hydrogen, a C 1 -C 12 alkyl that is unsubstituted or is substituted with hydroxyl; each X 1 and X 2 are independently a hydrolyzable substituent; and the reaction product is a silica-based fluorescent nanoparticle.

1 . A composition comprising:
 the reaction product of:
 an organic silane of Formula SiR 1   m X 1   4-m ; 
 a fluorescent dye-silane compound of Formula D-L 1 -(CH 2 ) n —SiX 2   3 ; 
 water; and 
 a hydrolysis catalyst; 
   wherein:
 R 1  is a C 1 -C 6  alkyl that is unsubstituted or substituted with one or more halogens or hydroxyl group, C 2 -C 6  alkenyl that is unsubstituted or substituted with one or more halogens or OH groups, or an aryl group that is unsubstituted or substituted with one or more halogens or OH groups; 
 m is 0 or 1; 
 n is 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, 
 D is a radical having a fluorophore; 
 L1 is a bond, O, S, C(O)O, C(O)NR 2 , SO 2 O, C(O)S, C(S), or S 2 ; 
 R 2  is hydrogen, or a C 1 -C 12  alkyl that is unsubstituted or is substituted with OH; 
 each X 1  and X 2  are independently a hydrolyzable substituent; and 
 the reaction product is a silica-based fluorescent nanoparticle comprising an outer surface comprising functional groups. 
   
     
     
         2 . The composition of  claim 1 , wherein 80% or more of the functional groups on the outer surface of the silica-based fluorescent nanoparticle are OH groups. 
     
     
         3 . The composition of  claim 1 , wherein D is a radical having a fluorophore derived from fluorescent dyes based on xanthene, benzo[a]xanthene, benzo[b]xanthene, benzo[c]xanthene, coumarin, benzocoumarin, alizarin, azo, phenoxazine, benzo[a]phenoxazine, benzo[b]phenoxazine, benzo[c]phenoxazine, naphthalimide, naphtholactam, azlactone, methyne, oxazine, thiazine, diketopyrrolopyrrole, quinacridone, thioepindoline, lactamimide, diphenylmaleimide, acetoacetamide, imidazothiazine, benzanthrone, phthalimide, benzotriazole, pyrimidine, pyrazine, or triazine. 
     
     
         4 . The composition of  claim 1 , wherein a surface of the silica-based fluorescent nanoparticle comprises, a group that is —OR 3  or —(CH 2 ) p Y bonded to a silicon atom;
 wherein:
 Y is NR 4 R 5 R 6 , PO 2 (OR 7 ), or —(OCH 2 CH 2 ) 4-15 OR 8 , 
 R 3 , R 4 , R 5 , R 6 , R 7 , and R 8  are each independently C 1 -C 8  alkyl; and 
 p is an integer from 1 to 15. 
   
     
     
         5 . The composition of  claim 1 , wherein 10% or less of the functional groups on the outer surface of the silica-based fluorescent nanoparticle are NH 2  groups. 
     
     
         6 . The composition of  claim 1 , wherein R 1  is methyl, ethyl, or phenyl. 
     
     
         7 . The composition of  claim 1 , wherein X 1  and X 2  are each independently halogen, C 1 -C 6  alkoxy, or C 1 -C 6  acyloxy. 
     
     
         8 . The composition of  claim 1 , wherein D is a radical represented by Formula I, Formula II, Formula III, or Formula IV: 
       
         
           
           
               
               
           
         
       
       wherein:
 A 1  is O, N-Z 1 , or NZ 1 Z 2 ; 
 Z 1  and Z 2  are each independently H or C 1 -C 8  alkyl, or Z 1  and R 12  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded, or Z 1  and R 14  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded, or Z 2  and R 14  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded; 
 A 2  is OZ 3  or NZ 4 Z 5 ; 
 Z 3  is H, C 1 -C 8  alkyl, or carboxy C 1 -C 8  alkyl; 
 Z 4  and Z 5  are each independently H or C 1 -C 8  alkyl, or Z 4  and R 13  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded, or Z 4  and R 17  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded, or Z 5  and R 17  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded; 
 q is an integer of 1 to 4, 
 R 11  is F, Cl, Br, I, CN, CF 3 , C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, phenyl, naphthyl, or a group of Formula 
 
       
         
           
           
               
               
           
         
         X 1 , X 2 , X 3 , X 4 , and X 5  are independently H, F, Cl, Br, I, CN, CF 3 , C 1 -C 8  alkyl, C 1 -C 8  alkoxy, C 1 -C 8  alkylthio, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 1 -C 8  alkylamido, SO 3 H, sulfonate, or CO 2 H, or X 1  and X 2 , X 2  and X 3 , X 3  and X 4 , or X 4  and X 5  join together form a phenyl group, together with the atoms to which they are bonded, which is unsubstituted or substituted with 1 to 4 F, Cl, Br, I, CN, CO 2 H, SO 3 H, OH, NH 2 , with unsubstituted or substituted mono- or di(C 1 -C 8  alkyl)amino, unsubstituted or substituted C 1 -C 8  alkyl, unsubstituted or substituted C 1 -C 8  alkylthio, or unsubstituted or substituted C 1 -C 8  alkoxy; 
         R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18  are independently H, F, Cl, Br, I, CN, CF 3 , unsubstituted or substituted C 1 -C 8  alkyl, unsubstituted or substituted C 1 -C 8  alkylthio, unsubstituted or substituted C 1 -C 8  alkoxy, phenyl, naphthyl, or heteroaryl, or R 14  and R 15 , or R 16  and R 17  join to form a benzo group. 
       
     
     
         9 . The composition of  claim 1 , wherein D is a coumarin radical represented by Formula V: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 20 , R 21 , R 22 , R 23 , R 24 , and R 25  are independently H, C 1 -C 8  alkyl, or NZ 6 Z 7 , 
 Z 6  and Z 7  are each independently H or C 1 -C 8  alkyl, or R 20  and Z 6 ; R 20  and Z 7 ; R 22  and Z 6 ; or R 22  and Z 7  join together to form a 5-, 6-, or 7-membered ring together with atoms to which they are bonded, that may be unsubstituted or substituted. 
 
     
     
         10 . The composition of  claim 1 , wherein ratio of the organic silane to the fluorescent dye-silane compound ranges from 1:1 to 100:1. 
     
     
         11 . A method of preparing a silica-based florescent nanoparticle, comprising:
 reacting a fluorescent dye of Formula D-A with a compound of Formula B—(CH 2 ) q′ —CH═CH 2  to produce a fluorescent dye derivative of Formula D-L1-(CH 2 ) q′ —CH═CH 2 ;   reacting the fluorescent dye derivative of Formula D-L1-(CH 2 ) q′ —CH═CH 2  with a silane compound of Formula HSiX 2   3  to produce a fluorescent dye-silane compound of Formula D-L 1 -(CH 2 ) n —SiX 2   3 : and   polymerizing an organic silane of Formula SiR 1   m′ X 1   4-m  and the fluorescent dye-silane compound of Formula D-L 1 -(CH 2 ) n —SiX 2   3  in the presence of water and a hydrolysis catalyst:
 wherein
 R 1  is a C 1 -C 6  alkyl that is unsubstituted or substituted with one or more halogens or hydroxyl group, C 2 -C 6  alkenyl that is unsubstituted or substituted with one or more halogens or hydroxyl group, or an aryl group that is unsubstituted or substituted with one or more halogens or hydroxyl group; 
 D is a radical having a fluorophore; 
 each X 1  and X 2  are independently a hydrolyzable substituent; 
 L1 is a bond, O, S, C(O)O, C(O)NR 2 , SO 2 O, C(O)S, C(S), or S 2 ; 
 A is COOH, OH, SO 3 H, CO—CH 2 -halogen, CH═CH 2  or SH; 
 B is OH, NHR 2 , F, Cl, Br, I, or SH; 
 q′ is an integer of 1 to 10; 
 n is an integer of 3 to 12; 
 m′ is 0 or 1; and 
 R 2  is hydrogen, C 1 -C 12  alkyl, or hydroxy-substituted C 1 -C 12  alkyl; 
 with the proviso that A and B are selected in such a manner as to be able to react with each other. 
 
   
     
     
         12 . The method of  claim 11 , wherein L 1  is C(O)O, A is C(O)OH, and B is F, Cl, Br, I, or OH. 
     
     
         13 . The method of  claim 11 , wherein the fluorescent dye derivative of Formula D-L1-(CH 2 ) q′ —CH═CH 2  is reacted with the silane compound of Formula HSiX 2   3  in a ratio of from 1:0.5 to 1:5. 
     
     
         14 . A compound represented by Formula D-L1-(CH 2 )q′-CH═CH 2  wherein:
 D is a radical having a fluorophore;   L1 is a bond, O, S, C(O)O, C(O)NR 2 , SO 2 O, C(O)S, C(S), or S 2 ; and   q′ is an integer of 1 to 10.   
     
     
         15 . The compound of  claim 14 , wherein D is a radical represented by Formula I, Formula II, Formula III, or Formula IV: 
       
         
           
           
               
               
           
         
       
       wherein:
 A 1  is O, N-Z 1 , or NZ 1 Z 2 ; 
 Z 1  and Z 2  are each independently H or C 1 -C 8  alkyl, or Z 1  and R 12  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded, or Z 1  and R 14  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded, or Z 2  and R 14  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded; 
 A 2  is OZ 3  or NZ 4 Z 5 ; 
 Z 3  is H, C 1 -C 8  alkyl, or carboxy C 1 -C 8  alkyl; 
 Z 4  and Z 5  are each independently H or C 1 -C 8  alkyl, or Z 4  and R 13  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded, or Z 4  and R 17  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded, or Z 5  and R 17  join together to form a 5-, 6-, or 7-membered ring together with the atoms to which they are bonded; 
 q is an integer of 1 to 4; 
 R 11  is F, Cl, Br, I, CN, CF 3 , C 1 -C 8  alkyl, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, phenyl, naphthyl, or a group of Formula 
 
       
         
           
           
               
               
           
         
         X 1 , X 2 , X 3 , X 4 , and X 5  are independently H, F, Cl, Br, I, CN, CF 3 , C 1 -C 8  alkyl, C 1 -C 8  alkoxy, C 1 -C 8  alkylthio, C 2 -C 8  alkenyl, C 2 -C 8  alkynyl, C 1 -C 8  alkylamido, SO 3 H, sulfonate, or CO 2 H, or X 1  and X 2 , X 2  and X 3 , X 3  and X 4 , or X 4  and X 5  join together form a phenyl group, together with the atoms to which they are bonded, which is unsubstituted or substituted with 1 to 4 F, Cl, Br, I, CN, CO 2 H, SO 3 H, OH, NH 2 , unsubstituted or substituted mono- or di(C 1 -C 8  alkyl)amino, unsubstituted or substituted C 1 -C 8  alkyl, unsubstituted or substituted C 1 -C 8  alkylthio, or unsubstituted or substituted C 1 -C 8  alkoxy; 
         R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18  are independently H, F, Cl, Br, I, CN, CF 3 , unsubstituted or substituted C 1 -C 8  alkyl, unsubstituted or substituted C 1 -C 8  alkylthio, unsubstituted or substituted C 1 -C 8  alkoxy, phenyl, naphthyl, or heteroaryl, or R 14  and R 15 , or R 16  and R 17  join to form a benzo group. 
       
     
     
         16 . The compound of  claim 14 , wherein, wherein D is a radical represented by Formula V: 
       
         
           
           
               
               
           
         
         wherein R 20 , R 21 , R 22 , R 23 , R 24 , and R 25  are independently H, C 1 -C 8  alkyl, or NZ 6 Z 7 , 
         Z 6  and Z 7  are each independently H or C 1 -C 8  alkyl, or R 20  and Z 6 ; R 20  and Z 7 ; R 22  and Z 6 ; or R 22  and Z 7  join together to form a 5-, 6-, or 7-membered ring together with atoms to which they are bonded, that may be unsubstituted or substituted. 
       
     
     
         17 . A colorant composition comprising the composition of  claim 1 . 
     
     
         18 . The colorant composition of  claim 17 , which includes a fluorescent ink, a fluorescent paint or a fluorescent paste. 
     
     
         19 . The colorant composition of  claim 17 , which is used as a biochemical marker. 
     
     
         20 . A method of coloring an article by using the composition of  claim 1 . 
     
     
         21 . A method of biochemically staining a cell by using the composition of  claim 1 .